ID MICU1_HUMAN Reviewed; 476 AA.
AC Q9BPX6; A8MV96; B3KN20; B4DJH9; B4DPI1; B5MBY3; D3YTJ3; O75785; Q9H9N6;
AC Q9UFX0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 27-MAR-2024, entry version 191.
DE RecName: Full=Calcium uptake protein 1, mitochondrial;
DE AltName: Full=Atopy-related autoantigen CALC {ECO:0000303|PubMed:16002733};
DE Short=ara CALC {ECO:0000303|PubMed:16002733};
DE AltName: Full=Calcium-binding atopy-related autoantigen 1 {ECO:0000303|PubMed:16002733};
DE AltName: Allergen=Hom s 4 {ECO:0000303|PubMed:16002733};
DE Flags: Precursor;
GN Name=MICU1; Synonyms=CALC {ECO:0000303|PubMed:16002733}, CBARA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 4 AND 5), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 159-476 (ISOFORM 2).
RC TISSUE=Kidney, Ovary, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 167-476 (ISOFORM 1), TISSUE SPECIFICITY, AND
RP ALLERGEN.
RX PubMed=9806765; DOI=10.1096/fasebj.12.14.1559;
RA Natter S., Seiberler S., Hufnagl P., Binder B.R., Hirschl A.M., Ring J.,
RA Abeck D., Schmidt T., Valent P., Valenta R.;
RT "Isolation of cDNA clones coding for IgE autoantigens with serum IgE from
RT atopic dermatitis patients.";
RL FASEB J. 12:1559-1569(1998).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16002733; DOI=10.4049/jimmunol.175.2.1286;
RA Aichberger K.J., Mittermann I., Reininger R., Seiberler S., Swoboda I.,
RA Spitzauer S., Kopp T., Stingl G., Sperr W.R., Valent P., Repa A., Bohle B.,
RA Kraft D., Valenta R.;
RT "Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of
RT calcium-binding proteins, can induce Th cell type 1-mediated
RT autoreactivity.";
RL J. Immunol. 175:1286-1294(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-231; GLU-242;
RP ASP-421 AND GLU-432.
RX PubMed=20693986; DOI=10.1038/nature09358;
RA Perocchi F., Gohil V.M., Girgis H.S., Bao X.R., McCombs J.E., Palmer A.E.,
RA Mootha V.K.;
RT "MICU1 encodes a mitochondrial EF hand protein required for Ca(2+)
RT uptake.";
RL Nature 467:291-296(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP INTERACTION WITH MCU.
RX PubMed=21685886; DOI=10.1038/nature10234;
RA Baughman J.M., Perocchi F., Girgis H.S., Plovanich M., Belcher-Timme C.A.,
RA Sancak Y., Bao X.R., Strittmatter L., Goldberger O., Bogorad R.L.,
RA Koteliansky V., Mootha V.K.;
RT "Integrative genomics identifies MCU as an essential component of the
RT mitochondrial calcium uniporter.";
RL Nature 476:341-345(2011).
RN [11]
RP FUNCTION, INTERACTION WITH MCU, AND MUTAGENESIS OF ASP-231; GLU-242;
RP ASP-421 AND GLU-432.
RX PubMed=23101630; DOI=10.1016/j.cell.2012.10.011;
RA Mallilankaraman K., Doonan P., Cardenas C., Chandramoorthy H.C., Muller M.,
RA Miller R., Hoffman N.E., Gandhirajan R.K., Molgo J., Birnbaum M.J.,
RA Rothberg B.S., Mak D.O., Foskett J.K., Madesh M.;
RT "MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+)
RT uptake that regulates cell survival.";
RL Cell 151:630-644(2012).
RN [12]
RP FUNCTION.
RX PubMed=22904319; DOI=10.1074/jbc.m112.392084;
RA Alam M.R., Groschner L.N., Parichatikanond W., Kuo L., Bondarenko A.I.,
RA Rost R., Waldeck-Weiermair M., Malli R., Graier W.F.;
RT "Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU)
RT contribute to metabolism-secretion coupling in clonal pancreatic beta-
RT cells.";
RL J. Biol. Chem. 287:34445-34454(2012).
RN [13]
RP INTERACTION WITH MCU.
RX PubMed=23178883; DOI=10.1038/ncb2622;
RA Mallilankaraman K., Cardenas C., Doonan P.J., Chandramoorthy H.C.,
RA Irrinki K.M., Golenar T., Csordas G., Madireddi P., Yang J., Muller M.,
RA Miller R., Kolesar J.E., Molgo J., Kaufman B., Hajnoczky G., Foskett J.K.,
RA Madesh M.;
RT "MCUR1 is an essential component of mitochondrial Ca(2+) uptake that
RT regulates cellular metabolism.";
RL Nat. Cell Biol. 14:1336-1343(2012).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23747253; DOI=10.1016/j.cmet.2013.04.020;
RA Csordas G., Golenar T., Seifert E.L., Kamer K.J., Sancak Y., Perocchi F.,
RA Moffat C., Weaver D., de la Fuente Perez S., Bogorad R., Koteliansky V.,
RA Adijanto J., Mootha V.K., Hajnoczky G.;
RT "MICU1 controls both the threshold and cooperative activation of the
RT mitochondrial Ca(2+) uniporter.";
RL Cell Metab. 17:976-987(2013).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MCU.
RX PubMed=24332854; DOI=10.1016/j.celrep.2013.11.026;
RA Hoffman N.E., Chandramoorthy H.C., Shamugapriya S., Zhang X., Rajan S.,
RA Mallilankaraman K., Gandhirajan R.K., Vagnozzi R.J., Ferrer L.M.,
RA Sreekrishnanilayam K., Natarajaseenivasan K., Vallem S., Force T.,
RA Choi E.T., Cheung J.Y., Madesh M.;
RT "MICU1 motifs define mitochondrial calcium uniporter binding and
RT activity.";
RL Cell Rep. 5:1576-1588(2013).
RN [16]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE UNIPLEX COMPLEX.
RX PubMed=24231807; DOI=10.1126/science.1242993;
RA Sancak Y., Markhard A.L., Kitami T., Kovacs-Bogdan E., Kamer K.J.,
RA Udeshi N.D., Carr S.A., Chaudhuri D., Clapham D.E., Li A.A., Calvo S.E.,
RA Goldberger O., Mootha V.K.;
RT "EMRE is an essential component of the mitochondrial calcium uniporter
RT complex.";
RL Science 342:1379-1382(2013).
RN [17]
RP FUNCTION.
RX PubMed=24313810; DOI=10.1042/bj20131025;
RA de la Fuente S., Matesanz-Isabel J., Fonteriz R.I., Montero M., Alvarez J.;
RT "Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells.";
RL Biochem. J. 458:33-40(2014).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF ASP-231; GLU-242; ASP-421 AND GLU-432.
RX PubMed=24503055; DOI=10.1002/embr.201337946;
RA Kamer K.J., Mootha V.K.;
RT "MICU1 and MICU2 play nonredundant roles in the regulation of the
RT mitochondrial calcium uniporter.";
RL EMBO Rep. 15:299-307(2014).
RN [19]
RP INTERACTION WITH SLC25A23.
RX PubMed=24430870; DOI=10.1091/mbc.e13-08-0502;
RA Hoffman N.E., Chandramoorthy H.C., Shanmughapriya S., Zhang X.Q.,
RA Vallem S., Doonan P.J., Malliankaraman K., Guo S., Rajan S., Elrod J.W.,
RA Koch W.J., Cheung J.Y., Madesh M.;
RT "SLC25A23 augments mitochondrial Ca(2+) uptake, interacts with MCU, and
RT induces oxidative stress-mediated cell death.";
RL Mol. Biol. Cell 25:936-947(2014).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MICU2.
RX PubMed=24560927; DOI=10.1016/j.molcel.2014.01.013;
RA Patron M., Checchetto V., Raffaello A., Teardo E., Vecellio Reane D.,
RA Mantoan M., Granatiero V., Szabo I., De Stefani D., Rizzuto R.;
RT "MICU1 and MICU2 finely tune the mitochondrial Ca(2+) uniporter by exerting
RT opposite effects on MCU activity.";
RL Mol. Cell 53:726-737(2014).
RN [21]
RP INVOLVEMENT IN MPXPS.
RX PubMed=24336167; DOI=10.1038/ng.2851;
RA Logan C.V., Szabadkai G., Sharpe J.A., Parry D.A., Torelli S., Childs A.M.,
RA Kriek M., Phadke R., Johnson C.A., Roberts N.Y., Bonthron D.T.,
RA Pysden K.A., Whyte T., Munteanu I., Foley A.R., Wheway G., Szymanska K.,
RA Natarajan S., Abdelhamed Z.A., Morgan J.E., Roper H., Santen G.W.,
RA Niks E.H., van der Pol W.L., Lindhout D., Raffaello A., De Stefani D.,
RA den Dunnen J.T., Sun Y., Ginjaar I., Sewry C.A., Hurles M., Rizzuto R.,
RA Duchen M.R., Muntoni F., Sheridan E.;
RT "Loss-of-function mutations in MICU1 cause a brain and muscle disorder
RT linked to primary alterations in mitochondrial calcium signaling.";
RL Nat. Genet. 46:188-193(2014).
RN [22]
RP SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, TRANSIT PEPTIDE, INTERACTION WITH
RP MICU2 AND CHCHD4, AND MUTAGENESIS OF CYS-463.
RX PubMed=26387864; DOI=10.1016/j.cmet.2015.08.019;
RA Petrungaro C., Zimmermann K.M., Kuettner V., Fischer M., Dengjel J.,
RA Bogeski I., Riemer J.;
RT "The Ca(2+)-dependent release of the Mia40-induced MICU1-MICU2 dimer from
RT MCU regulates mitochondrial Ca(2+) uptake.";
RL Cell Metab. 22:721-733(2015).
RN [23]
RP INTERACTION WITH MCU.
RX PubMed=26341627; DOI=10.15252/embr.201540436;
RA Lee Y., Min C.K., Kim T.G., Song H.K., Lim Y., Kim D., Shin K., Kang M.,
RA Kang J.Y., Youn H.S., Lee J.G., An J.Y., Park K.R., Lim J.J., Kim J.H.,
RA Kim J.H., Park Z.Y., Kim Y.S., Wang J., Kim D.H., Eom S.H.;
RT "Structure and function of the N-terminal domain of the human mitochondrial
RT calcium uniporter.";
RL EMBO Rep. 16:1318-1333(2015).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [25]
RP SUBUNIT.
RX PubMed=26489515; DOI=10.1038/srep15602;
RA Waldeck-Weiermair M., Malli R., Parichatikanond W., Gottschalk B.,
RA Madreiter-Sokolowski C.T., Klec C., Rost R., Graier W.F.;
RT "Rearrangement of MICU1 multimers for activation of MCU is solely
RT controlled by cytosolic Ca(2.).";
RL Sci. Rep. 5:15602-15602(2015).
RN [26]
RP FUNCTION.
RX PubMed=26903221; DOI=10.1016/j.bbamem.2016.02.022;
RA Matesanz-Isabel J., Arias-Del-Val J., Alvarez-Illera P., Fonteriz R.I.,
RA Montero M., Alvarez J.;
RT "Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake.";
RL Biochim. Biophys. Acta 1858:1110-1117(2016).
RN [27]
RP SUBCELLULAR LOCATION.
RX PubMed=26774479; DOI=10.1016/j.celrep.2015.12.054;
RA Vais H., Mallilankaraman K., Mak D.O., Hoff H., Payne R., Tanis J.E.,
RA Foskett J.K.;
RT "EMRE is a matrix Ca(2+) sensor that governs gatekeeping of the
RT mitochondrial Ca(2+) uniporter.";
RL Cell Rep. 14:403-410(2016).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMDT1, AND MUTAGENESIS OF
RP 99-LYS--LYS-102.
RX PubMed=27099988; DOI=10.7554/elife.15545;
RA Tsai M.F., Phillips C.B., Ranaghan M., Tsai C.W., Wu Y., Willliams C.,
RA Miller C.;
RT "Dual functions of a small regulatory subunit in the mitochondrial calcium
RT uniporter complex.";
RL Elife 5:0-0(2016).
RN [29]
RP INVOLVEMENT IN A SYNDROME CAUSING FATIGUE AND LETHARGY IN CHILDHOOD.
RX PubMed=27123478; DOI=10.1212/nxg.0000000000000059;
RA Lewis-Smith D., Kamer K.J., Griffin H., Childs A.M., Pysden K., Titov D.,
RA Duff J., Pyle A., Taylor R.W., Yu-Wai-Man P., Ramesh V., Horvath R.,
RA Mootha V.K., Chinnery P.F.;
RT "Homozygous deletion in MICU1 presenting with fatigue and lethargy in
RT childhood.";
RL Neurol. Genet. 2:E59-E59(2016).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 97-476, X-RAY CRYSTALLOGRAPHY (2.7
RP ANGSTROMS) OF 97-444 IN COMPLEX WITH CALCIUM, SUBUNIT, CALCIUM-BINDING
RP SITES, AND MUTAGENESIS OF ARG-221; ASP-376 AND 383-PHE--HIS-385.
RX PubMed=24514027; DOI=10.1002/embj.201386523;
RA Wang L., Yang X., Li S., Wang Z., Liu Y., Feng J., Zhu Y., Shen Y.;
RT "Structural and mechanistic insights into MICU1 regulation of mitochondrial
RT calcium uptake.";
RL EMBO J. 33:594-604(2014).
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) that
CC senses calcium level via its EF-hand domains (PubMed:20693986,
CC PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854,
CC PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221,
CC PubMed:27099988). MICU1 and MICU2 form a disulfide-linked heterodimer
CC that stimulates and inhibits MCU activity, depending on the
CC concentration of calcium. MICU1 acts both as an activator or inhibitor
CC of mitochondrial calcium uptake (PubMed:26903221). Acts as a gatekeeper
CC of MCU at low concentration of calcium, preventing channel opening
CC (PubMed:26903221). Enhances MCU opening at high calcium concentration,
CC allowing a rapid response of mitochondria to calcium signals generated
CC in the cytoplasm (PubMed:24560927, PubMed:26903221). Regulates glucose-
CC dependent insulin secretion in pancreatic beta-cells by regulating
CC mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-
CC mediated autoreactivity, which is accompanied by the release of IFNG
CC (PubMed:16002733). {ECO:0000269|PubMed:16002733,
CC ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:22904319,
CC ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:23747253,
CC ECO:0000269|PubMed:24313810, ECO:0000269|PubMed:24332854,
CC ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927,
CC ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26903221,
CC ECO:0000269|PubMed:27099988}.
CC -!- SUBUNIT: Homohexamer; in absence of calcium (PubMed:24514027). Forms a
CC homohexamer in absence of calcium and rearranges into a heterodimer in
CC presence of calcium (PubMed:26489515, PubMed:24514027). Heterodimer;
CC disulfide-linked; heterodimerizes with MICU2 (PubMed:24560927). The
CC heterodimer formed with MICU2 associates with MCU at low calcium
CC concentration and dissociates from MCU at high calcium level
CC (PubMed:26387864). Component of the uniplex complex, composed of MCU,
CC MCUB, MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807). Interacts (via
CC polybasic region) with EMRE/SMDT1; the interaction is direct
CC (PubMed:27099988). Interacts (via polybasic region) with MCU (via
CC coiled coil domains); the interaction is direct and precedes formation
CC of the heterodimer with MICU2 (PubMed:21685886, PubMed:23101630,
CC PubMed:23178883, PubMed:24332854, PubMed:26387864). Interacts with
CC SLC25A23 (PubMed:24430870). Interacts with CHCHD4/MIA40; which
CC introduces the interchain disulfide bond with MICU2 (PubMed:26387864).
CC {ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:23101630,
CC ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:24231807,
CC ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24430870,
CC ECO:0000269|PubMed:24514027, ECO:0000269|PubMed:24560927,
CC ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26489515,
CC ECO:0000269|PubMed:27099988}.
CC -!- INTERACTION:
CC Q9BPX6; Q8N4Q1: CHCHD4; NbExp=6; IntAct=EBI-2371996, EBI-2562213;
CC Q9BPX6; Q8NE86: MCU; NbExp=7; IntAct=EBI-2371996, EBI-6552124;
CC Q9BPX6; Q8NE86-1: MCU; NbExp=2; IntAct=EBI-2371996, EBI-15932889;
CC Q9BPX6; Q9BPX6: MICU1; NbExp=8; IntAct=EBI-2371996, EBI-2371996;
CC Q9BPX6; Q8IYU8: MICU2; NbExp=5; IntAct=EBI-2371996, EBI-3197790;
CC Q9BPX6-1; Q8NE86-1: MCU; NbExp=2; IntAct=EBI-5456336, EBI-15932889;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:24332854,
CC ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26774479,
CC ECO:0000269|PubMed:27099988, ECO:0000305|PubMed:24231807}; Single-pass
CC membrane protein {ECO:0000255}. Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24560927,
CC ECO:0000269|PubMed:26387864}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9BPX6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BPX6-2; Sequence=VSP_031980, VSP_031981;
CC Name=3;
CC IsoId=Q9BPX6-3; Sequence=VSP_031979;
CC Name=4;
CC IsoId=Q9BPX6-4; Sequence=VSP_039890, VSP_039891;
CC Name=5;
CC IsoId=Q9BPX6-5; Sequence=VSP_039890, VSP_039892;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cell lines. Strongly
CC expressed in epidermal keratinocytes and dermal endothelial cells.
CC {ECO:0000269|PubMed:16002733, ECO:0000269|PubMed:9806765}.
CC -!- DOMAIN: The C-helix is required for assembling the Ca(2+)-free
CC homohexamer (PubMed:24514027). It also plays a key role in
CC mitochondrial calcium uptake, probably by mediating interaction with
CC MICU2 (PubMed:24503055, PubMed:24514027). {ECO:0000269|PubMed:24503055,
CC ECO:0000269|PubMed:24514027}.
CC -!- DOMAIN: The EF-hand domains have high affinity for calcium and act as
CC sensors of calcium levels (PubMed:23101630, PubMed:24560927).
CC {ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24560927}.
CC -!- DISEASE: Myopathy with extrapyramidal signs (MPXPS) [MIM:615673]: An
CC autosomal recessive disorder characterized by early-onset proximal
CC muscle weakness with a static course and moderately to grossly elevated
CC serum creatine kinase levels accompanied by learning difficulties. Most
CC patients develop subtle extrapyramidal motor signs that progress to a
CC debilitating disorder of involuntary movement with variable features,
CC including chorea, tremor, dystonic posturing and orofacial dyskinesia.
CC Additional variable features include ataxia, microcephaly,
CC ophthalmoplegia, ptosis, optic atrophy and axonal peripheral
CC neuropathy. {ECO:0000269|PubMed:24336167}. Note=The disease is caused
CC by variants affecting the gene represented in this entry. The complex
CC phenotype is due to alterations in mitochondrial calcium signaling
CC characterized by increased mitochondrial Ca(2+) load (PubMed:24336167).
CC {ECO:0000269|PubMed:24336167}.
CC -!- DISEASE: Note=An homozygous partial MICU1 deletion is responsible for a
CC disorder manifesting in childhood with fatigue, lethargy and muscle
CC weakness. The disease is caused by variants affecting the gene
CC represented in this entry. {ECO:0000269|PubMed:27123478}.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE from
CC atopic dermatitis (AD) patients. Identified as an IgE autoantigen in
CC atopic dermatitis (AD) patients with severe skin manifestations.
CC {ECO:0000269|PubMed:9806765}.
CC -!- SIMILARITY: Belongs to the MICU1 family. MICU1 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Was initially thought to act as an inhibitor of MCU based on
CC effects following MICU1 depletion (PubMed:20693986, PubMed:23101630).
CC However, depletion of MICU1 also eliminates MICU2, explaining the
CC initial conclusion. It was later shown to act as a stimulator of MCU
CC activity instead (PubMed:24560927). {ECO:0000305|PubMed:20693986,
CC ECO:0000305|PubMed:23101630, ECO:0000305|PubMed:24560927}.
CC -!- CAUTION: The topology is subject to discussion. According to some
CC reports, localizes at the outer surface of the mitochondrion inner
CC membrane (PubMed:20693986, PubMed:24332854). According to another
CC publication, forms an intramembrane hairpin loop without crossing the
CC membrane (PubMed:23747253). Recent studies rather suggest that it
CC contains a transmembrane region that crosses the mitochondrial inner
CC membrane, with the main part of the protein localized in the
CC mitochondrial intermembrane space (PubMed:26387864, PubMed:26489515).
CC {ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23747253,
CC ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:26387864,
CC ECO:0000269|PubMed:26489515}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14187.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA76830.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AK023318; BAG51182.1; -; mRNA.
DR EMBL; AK296086; BAG58841.1; -; mRNA.
DR EMBL; AK298347; BAG60593.1; -; mRNA.
DR EMBL; AL117423; CAB55915.1; -; mRNA.
DR EMBL; AC091769; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL513185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54459.1; -; Genomic_DNA.
DR EMBL; BC004190; AAH04190.1; -; mRNA.
DR EMBL; BC004216; AAH04216.1; -; mRNA.
DR EMBL; BC016641; AAH16641.1; -; mRNA.
DR EMBL; AK022697; BAB14187.1; ALT_INIT; mRNA.
DR EMBL; Y17711; CAA76830.1; ALT_SEQ; mRNA.
DR CCDS; CCDS55714.1; -. [Q9BPX6-4]
DR CCDS; CCDS55715.1; -. [Q9BPX6-1]
DR PIR; T17225; T17225.
DR RefSeq; NP_001182447.1; NM_001195518.1. [Q9BPX6-1]
DR RefSeq; NP_001182448.1; NM_001195519.1. [Q9BPX6-4]
DR RefSeq; NP_006068.2; NM_006077.3. [Q9BPX6-3]
DR PDB; 4NSC; X-ray; 3.20 A; A/B/C/D/E/F=97-476.
DR PDB; 4NSD; X-ray; 2.70 A; A/B=97-444.
DR PDB; 6K7Y; EM; 3.60 A; I/V=1-476.
DR PDB; 6LB7; X-ray; 2.10 A; A/C=97-444.
DR PDB; 6LB8; X-ray; 3.28 A; A/C=97-444.
DR PDB; 6LE5; X-ray; 3.10 A; A/D/E/G=97-444.
DR PDB; 6WDN; EM; 3.20 A; B=104-466.
DR PDB; 6WDO; EM; 3.60 A; Q/S=104-442.
DR PDB; 6XJV; EM; 4.17 A; Q/S=1-476.
DR PDB; 6XJX; EM; 4.60 A; Q=1-476.
DR PDB; 6XQN; EM; 3.30 A; I=94-476.
DR PDB; 6XQO; EM; 3.10 A; I=94-476.
DR PDBsum; 4NSC; -.
DR PDBsum; 4NSD; -.
DR PDBsum; 6K7Y; -.
DR PDBsum; 6LB7; -.
DR PDBsum; 6LB8; -.
DR PDBsum; 6LE5; -.
DR PDBsum; 6WDN; -.
DR PDBsum; 6WDO; -.
DR PDBsum; 6XJV; -.
DR PDBsum; 6XJX; -.
DR PDBsum; 6XQN; -.
DR PDBsum; 6XQO; -.
DR AlphaFoldDB; Q9BPX6; -.
DR EMDB; EMD-21642; -.
DR EMDB; EMD-21643; -.
DR EMDB; EMD-22215; -.
DR EMDB; EMD-22216; -.
DR EMDB; EMD-22290; -.
DR EMDB; EMD-22291; -.
DR EMDB; EMD-9945; -.
DR SMR; Q9BPX6; -.
DR BioGRID; 115646; 79.
DR ComplexPortal; CPX-5961; Mitochondrial calcium uniporter complex, MICU1-MICU2 variant.
DR ComplexPortal; CPX-5963; Mitochondrial calcium uniporter complex, MICU1 variant.
DR ComplexPortal; CPX-5965; Mitochondrial calcium uniporter complex, MICU1-MICU3 variant.
DR ComplexPortal; CPX-5966; Mitochondrial calcium uniporter complex, MICUB variant.
DR CORUM; Q9BPX6; -.
DR DIP; DIP-53438N; -.
DR IntAct; Q9BPX6; 40.
DR MINT; Q9BPX6; -.
DR STRING; 9606.ENSP00000493232; -.
DR Allergome; 3325; Hom s 4.0101.
DR Allergome; 414; Hom s 4.
DR TCDB; 8.A.44.1.1; the mitochondrial ef hand ca(2+) uniporter regulator (micu) family.
DR iPTMnet; Q9BPX6; -.
DR PhosphoSitePlus; Q9BPX6; -.
DR SwissPalm; Q9BPX6; -.
DR BioMuta; MICU1; -.
DR DMDM; 74761192; -.
DR EPD; Q9BPX6; -.
DR jPOST; Q9BPX6; -.
DR MassIVE; Q9BPX6; -.
DR MaxQB; Q9BPX6; -.
DR PaxDb; 9606-ENSP00000354415; -.
DR PeptideAtlas; Q9BPX6; -.
DR ProteomicsDB; 78588; -. [Q9BPX6-1]
DR ProteomicsDB; 78589; -. [Q9BPX6-2]
DR ProteomicsDB; 78590; -. [Q9BPX6-3]
DR ProteomicsDB; 78591; -. [Q9BPX6-4]
DR ProteomicsDB; 78592; -. [Q9BPX6-5]
DR Pumba; Q9BPX6; -.
DR Antibodypedia; 29257; 219 antibodies from 29 providers.
DR DNASU; 10367; -.
DR Ensembl; ENST00000361114.10; ENSP00000354415.5; ENSG00000107745.20. [Q9BPX6-1]
DR Ensembl; ENST00000398763.8; ENSP00000381747.4; ENSG00000107745.20. [Q9BPX6-5]
DR Ensembl; ENST00000418483.6; ENSP00000402470.2; ENSG00000107745.20. [Q9BPX6-4]
DR GeneID; 10367; -.
DR KEGG; hsa:10367; -.
DR MANE-Select; ENST00000361114.10; ENSP00000354415.5; NM_001195518.2; NP_001182447.1.
DR UCSC; uc001jtb.3; human. [Q9BPX6-1]
DR AGR; HGNC:1530; -.
DR CTD; 10367; -.
DR DisGeNET; 10367; -.
DR GeneCards; MICU1; -.
DR HGNC; HGNC:1530; MICU1.
DR HPA; ENSG00000107745; Low tissue specificity.
DR MalaCards; MICU1; -.
DR MIM; 605084; gene.
DR MIM; 615673; phenotype.
DR neXtProt; NX_Q9BPX6; -.
DR OpenTargets; ENSG00000107745; -.
DR Orphanet; 401768; Proximal myopathy with extrapyramidal signs.
DR PharmGKB; PA26110; -.
DR VEuPathDB; HostDB:ENSG00000107745; -.
DR eggNOG; KOG2643; Eukaryota.
DR GeneTree; ENSGT00950000183079; -.
DR HOGENOM; CLU_027103_3_1_1; -.
DR InParanoid; Q9BPX6; -.
DR OMA; GGPMYMT; -.
DR OrthoDB; 1020411at2759; -.
DR PhylomeDB; Q9BPX6; -.
DR TreeFam; TF313815; -.
DR PathwayCommons; Q9BPX6; -.
DR Reactome; R-HSA-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-HSA-8949664; Processing of SMDT1.
DR SignaLink; Q9BPX6; -.
DR SIGNOR; Q9BPX6; -.
DR BioGRID-ORCS; 10367; 18 hits in 1153 CRISPR screens.
DR ChiTaRS; MICU1; human.
DR GeneWiki; CBARA1; -.
DR GenomeRNAi; 10367; -.
DR Pharos; Q9BPX6; Tbio.
DR PRO; PR:Q9BPX6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9BPX6; Protein.
DR Bgee; ENSG00000107745; Expressed in calcaneal tendon and 202 other cell types or tissues.
DR ExpressionAtlas; Q9BPX6; baseline and differential.
DR Genevisible; Q9BPX6; HS.
DR GO; GO:0034704; C:calcium channel complex; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:1990246; C:uniplex complex; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IDA:ComplexPortal.
DR GO; GO:0070509; P:calcium ion import; IDA:UniProtKB.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IDA:ComplexPortal.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:1900069; P:regulation of cellular hyperosmotic salinity response; IMP:UniProtKB.
DR CDD; cd16173; EFh_MICU1; 1.
DR Gene3D; 1.10.238.10; EF-hand; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR039800; MICU1/2/3.
DR PANTHER; PTHR12294:SF1; CALCIUM UPTAKE PROTEIN 1, MITOCHONDRIAL; 1.
DR PANTHER; PTHR12294; EF HAND DOMAIN FAMILY A1,A2-RELATED; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; EF-hand; 2.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Allergen; Alternative splicing; Calcium; Calcium transport;
KW Disulfide bond; Ion transport; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26387864"
FT CHAIN 34..476
FT /note="Calcium uptake protein 1, mitochondrial"
FT /id="PRO_0000322990"
FT TRANSMEM 34..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..476
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:26387864"
FT DOMAIN 218..253
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 408..443
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 68..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..110
FT /note="Polybasic region"
FT /evidence="ECO:0000269|PubMed:27099988"
FT REGION 455..465
FT /note="C-helix region"
FT /evidence="ECO:0000269|PubMed:24514027"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 421
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 423
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 425
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 427
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:24514027"
FT DISULFID 463
FT /note="Interchain (with C-413 in MICU2)"
FT /evidence="ECO:0000305|PubMed:26387864"
FT VAR_SEQ 1..198
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039890"
FT VAR_SEQ 179
FT /note="K -> KTE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11230166"
FT /id="VSP_031979"
FT VAR_SEQ 199..218
FT /note="GECGLISFSDYIFLTTVLST -> MKRIYTYRRAKEIFKDTPKA (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039891"
FT VAR_SEQ 199..218
FT /note="GECGLISFSDYIFLTTVLST -> MVSLKAKLNHLRQSMLKQKA (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039892"
FT VAR_SEQ 394..403
FT /note="VTMQQVARTV -> GKGTIFMGRR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031980"
FT VAR_SEQ 404..476
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031981"
FT MUTAGEN 99..102
FT /note="KKKK->EQEQ: Abolishes interaction with EMRE/SMDT1
FT while maintaining interaction with MICU2SO."
FT /evidence="ECO:0000269|PubMed:27099988"
FT MUTAGEN 221
FT /note="R->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:24514027"
FT MUTAGEN 231
FT /note="D->A: Abolishes mitochondrial Ca(2+) uptake; when
FT associated with A-242; A-421 and A-432."
FT /evidence="ECO:0000269|PubMed:20693986,
FT ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"
FT MUTAGEN 242
FT /note="E->A,K: Abolishes mitochondrial Ca(2+) uptake; when
FT associated with A-231; A-421 and A-432."
FT /evidence="ECO:0000269|PubMed:20693986,
FT ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"
FT MUTAGEN 376
FT /note="D->A: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:24514027"
FT MUTAGEN 383..385
FT /note="FYH->AYA: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:24514027"
FT MUTAGEN 421
FT /note="D->A: Abolishes mitochondrial Ca(2+) uptake; when
FT associated with A-231; A-242 and A-432."
FT /evidence="ECO:0000269|PubMed:20693986,
FT ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"
FT MUTAGEN 432
FT /note="E->A: Abolishes mitochondrial Ca(2+) uptake; when
FT associated with A-231; A-242 and A-421."
FT /evidence="ECO:0000269|PubMed:20693986,
FT ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"
FT MUTAGEN 432
FT /note="E->K: Loss of function; when associated with A-421."
FT /evidence="ECO:0000269|PubMed:20693986,
FT ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"
FT MUTAGEN 463
FT /note="C->A: Abolishes interchain disulfide bond and
FT heterodimer formation with MICU2."
FT /evidence="ECO:0000269|PubMed:26387864"
FT CONFLICT 54
FT /note="R -> G (in Ref. 2; CAB55915)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="K -> E (in Ref. 1; BAG60593)"
FT /evidence="ECO:0000305"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 124..131
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 149..155
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:6LE5"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:4NSC"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6XQN"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:6WDN"
FT HELIX 194..198
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:6LE5"
FT HELIX 206..217
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 220..230
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 231..238
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 240..253
FT /evidence="ECO:0007829|PDB:6LB7"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:4NSC"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6WDN"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:6LB7"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:4NSD"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:6LB8"
FT HELIX 293..314
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 324..335
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 340..352
FT /evidence="ECO:0007829|PDB:6LB7"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 361..372
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 374..380
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 382..386
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 393..403
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 410..420
FT /evidence="ECO:0007829|PDB:6LB7"
FT STRAND 425..428
FT /evidence="ECO:0007829|PDB:6LB7"
FT TURN 430..433
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 434..438
FT /evidence="ECO:0007829|PDB:6LB7"
FT HELIX 455..464
FT /evidence="ECO:0007829|PDB:4NSC"
SQ SEQUENCE 476 AA; 54351 MW; D83C3A38F4B28FDF CRC64;
MFRLNSLSAL AELAVGSRWY HGGSQPIQIR RRLMMVAFLG ASAVTASTGL LWKRAHAESP
PCVDNLKSDI GDKGKNKDEG DVCNHEKKTA DLAPHPEEKK KKRSGFRDRK VMEYENRIRA
YSTPDKIFRY FATLKVISEP GEAEVFMTPE DFVRSITPNE KQPEHLGLDQ YIIKRFDGKK
ISQEREKFAD EGSIFYTLGE CGLISFSDYI FLTTVLSTPQ RNFEIAFKMF DLNGDGEVDM
EEFEQVQSII RSQTSMGMRH RDRPTTGNTL KSGLCSALTT YFFGADLKGK LTIKNFLEFQ
RKLQHDVLKL EFERHDPVDG RITERQFGGM LLAYSGVQSK KLTAMQRQLK KHFKEGKGLT
FQEVENFFTF LKNINDVDTA LSFYHMAGAS LDKVTMQQVA RTVAKVELSD HVCDVVFALF
DCDGNGELSN KEFVSIMKQR LMRGLEKPKD MGFTRLMQAM WKCAQETAWD FALPKQ
//
